Multi-functional graphene as an in vitro and in vivo imaging probe

Multi-functional graphene as an in vitro and in vivo imaging probe
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DOI:
10.1016/j.biomaterials.2011.12.010
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发表时间:
2012-03-01
期刊:
影响因子:
14
通讯作者:
Ling, Yong-Chien
Ling, Yong-Chien
中科院分区:
工程技术1区
文献类型:
--
作者:
Gollavelli, Ganesh;Ling, Yong-Chien

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采用绿色合成方法合成了多功能石墨烯(MFG),并探讨了其作为一种有前途的荧光标记物在体内外成像中的生物医学应用。采用原位微波辅助还原和磁化过程,在1 min内将氧化石墨烯转化为磁性石墨烯,其进一步共价修饰以构建用于连接荧光素邻甲基丙烯酸酯(FMA)的聚丙烯酸(PAA)桥,从而得到具有水溶性(类似于2.5 g/l)和荧光性质(最大发射波长为526 nm)的MFG。PAA桥还起到防止石墨烯诱导的缀合的FMA的荧光淬灭的作用。用TEM、AFM、拉曼、XPS、FT-IR、TGA和SQUID测量证实了还原、磁化和官能化的程度。HeLa细胞的体外细胞毒性研究表明,MFG可以作为一种生物相容性成像探针,IC 50值为100 μ g/ml;而在体内斑马鱼的研究没有引起任何显着的异常,也不影响显微注射后的存活率。共聚焦激光扫描显微镜图像显示,MFG仅定位于细胞质区域,在斑马鱼中表现出良好的共定位和从头到尾的生物分布。我们的结果证明了基于石墨烯的荧光标记物用于细胞内成像的适用性,更重要的是,以及整个动物成像。因此,MFG可以优先用作生物医学诊断中的双功能探针。(C)2011爱思唯尔有限公司保留所有权利。
A strategy has been developed for the synthesis of multi-functional graphene (MFG) using green synthetic approach and explored its biomedical application as a promising fluorescent marker for in vitro and in vivo imaging. In-situ microwave-assisted reduction and magnetization process was adopted to convert the graphene oxide into magnetic graphene within 1 min, which was further covalently modified to build a polyacrylic acid (PAA) bridge for linking the fluorescein o-methacrylate (FMA) to yield MFG with water-dispersibility (similar to 2.5 g/l) and fluorescence property (emission maximum at 526 nm). The PAA bridges also functions to prevent graphene-induced fluorescence quenching of conjugated FMA. The extent of reduction, magnetization, and functionalization was confirmed with TEM, AFM, Raman, XPS, FT-IR, TGA, and SQUID measurements. In vitro cytotoxicity study of HeLa cells reveal that MFG could stand as a biocompatible imaging probe with an IC50 value of 100 mu g/ml; whereas in vivo zebrafish study does not induce any significant abnormalities nor affects the survival rate after microinjection of MFG. Confocal laser scanning microscopy images reveals that MFG locates only in the cytoplasm region and exhibits excellent co-localization and biodistribution from the head to tail in the zebrafish. Our results demonstrate the applicability of graphene based fluorescence marker for intracellular imaging and, more significantly, as well as whole-animal imaging. Hence, MFG could preferentially serve as a dual functional probe in biomedical diagnostics. (C) 2011 Elsevier Ltd. All rights reserved.